Acetaminophen (Molecule of the Month for June 2003)
Paracetamol, Panadol, Tylenol
Papa-amino-phenol , a parent compound of acetoaminophen, was discovered to reduce fever in the late 1800s. However, due to its high toxicity, it was useless in medicine. It was discovered that acetophenetidin (phenacetin), which is less toxic, was an equally effective antipyretic agent which also possessed analgesic (pain-relieving) properties.
Phenacetin soon became a commonly used ingredient of analgesic-antipyretic medications until later on, in 1949, when it was found that phenacetin is converted in the body to an even less toxic metabolite, acetaminophen. From then on, acetaminophen gradually replaced phenacetin as a popular analgesic. It is now widely available as an ingredient in many non-prescription drugs to relive migraines and tension headaches.
Acetaminophen is completely absorbed from the gastrointestinal tract and, after oral administration, peak plasma concentrations are reached in less than an hour. The drug is fairly uniformly distributed in the body and approximately 90% of a therapeutic dose is eliminated by conjugation with glucoronic acid in the liver ; 3-5% is catabolized to the acid and cysteine conjugates by the P-450 mixed function oxidase enzyme system . All of these metabolites are excreted in the urine and in fact only a slight amount of the drug is excreted unchanged. It is the intermediate metabolites formed during the biotransformation in the liver (whose structures are uncertain) that are believed to be responsible for the hepatotoxicity of the drug.
The biologic half-life of acetaminophen in normal adults is about 2-3 hours. Because the hepatic conjugation is the rate-determining step in the catabolic pathway, the half-life is found to be longer in patients with liver disease or in the presence of other drugs which compete for the hepatic conjugation mechanism.
Acetaminophen does not have anti-inflammatory activity and it does not effect blood clotting (homeostasis). Its pain relieving ability is about equal to that of aspirin and it is preferred over aspirin when the homeostatic side effects of aspirin must be avoided.
Formal Chemical Name (IUPAC)
Update by Karl Harrison
(Molecule of the Month for June 2003 )
All the images on this web site are are made available with a Creative Commons Attribution license and so can be used as long as the attribution © Karl Harrison 3DChem.com is written with the image. High resolution images and illustrations are available on request.